Zika Virus and Neuropathogenesis: The Unanswered Question of Which Strain Is More Prone to Causing Microcephaly and
Emily Louise King1, Nerea Irigoyen1
1Division of Virology, Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
Abstract:
Despite being perceived to be a relatively innocuous pathogen during its circulation in Africa in the 20th century, consequent outbreaks in French Polynesia and Latin America revealed the Zika virus (ZIKV) to be capable of causing severe neurological defects. Foetuses infected with the virus during pregnancy developed a range of pathologies including microcephaly, cerebral calcifications and macular scarring. These are now collectively known as Congenital Zika syndrome (CZS). It has been established that the neuropathogenesis of ZIKV results from infection of neural progenitor cells in the developing cerebral cortex. Following this, two main hypotheses have emerged: the virus causes either apoptosis or premature differentiation of neural progenitor cells, reducing the final number of mature neurons in the cerebral cortex. This review describes the cellular processes which could potentially cause virus induced apoptosis or premature differentiation, leading to speculation that a combination of the two may be responsible for the pathologies associated with ZIKV. The review also discusses which specific lineages of the ZIKV can employ these mechanisms. It has been unclear in the past whether the virus evolved its neurotropic capability following circulation in Africa, or if the virus has always caused microcephaly but public health surveillance in Africa had failed to detect it. Understanding the true neuropathogenesis of ZIKV is key to being prepared for further outbreaks in the future, and it will also provide insight into how neurotropic viruses can cause profound and life-long neurological defects.
Insights
Zika virus (ZIKV) can cause severe neurological defects like microcephaly, known as Congenital Zika syndrome (CZS). This review explores how ZIKV infects brain cells, potentially causing apoptosis or premature differentiation, leading to these birth defects.
Area of Science:
- Neuroscience
- Virology
- Developmental Biology
Background:
- Zika virus (ZIKV) outbreaks revealed severe neurological defects, particularly Congenital Zika syndrome (CZS) in foetuses.
- CZS includes microcephaly, cerebral calcifications, and macular scarring, linked to ZIKV infection of neural progenitor cells.
Purpose of the Study:
- To review the cellular mechanisms of ZIKV neuropathogenesis.
- To investigate how ZIKV infection leads to apoptosis or premature differentiation of neural progenitor cells.
- To discuss ZIKV lineages and their potential neurotropic evolution.
Main Methods:
- Literature review of cellular processes in ZIKV-induced neuropathogenesis.
- Analysis of hypotheses regarding ZIKV's impact on neural progenitor cells.
- Discussion of viral evolution and public health surveillance data.
Main Results:
- ZIKV infection targets neural progenitor cells in the developing cerebral cortex.
- Two primary hypotheses suggest ZIKV induces apoptosis or premature differentiation.
- A combination of these mechanisms may explain CZS pathologies.
Conclusions:
- Understanding ZIKV neuropathogenesis is crucial for future outbreak preparedness.
- ZIKV's neurotropic capabilities and evolutionary history require further investigation.
- Insights into ZIKV can illuminate mechanisms of other neurotropic viruses.
